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United States • Title 21 CFR • Part 355
This part establishes the conditions under which over-the-counter (OTC) anticaries drug products are generally recognized as safe and effective (GRASE) and not misbranded. It covers scope, definitions, approved active ingredients, packaging, labeling, and testing procedures for fluoride-containing dental products.
(a) An over-the-counter anticaries drug product in a form suitable for topical administration to the teeth is generally recognized as safe and effective and is not misbranded if it meets each condition in this part and each general condition established in § 330.1 of this chapter. (b) References in this part to regulatory sections of the Code of Federal Regulations are to chapter I of title 21 unless otherwise noted.
The active ingredient of the product consists of any of the following when used in the concentration and dosage form established for each ingredient: Sodium fluorideDentifrices containing 850 to 1,150 ppm theoretical total fluorine in a gel or paste dosage form.(a) —(1) Sodium fluoride 0.188 to 0.254 percent with an available fluoride ion concentration ≥650 parts per million (ppm). Dentifrices containing 850 to 1,150 ppm theoretical total fluorine in a powdered dosage form.(2) Sodium fluoride 0.188 to 0.254 percent with an available fluoride ion concentration of ≥850 ppm for products containing the abrasive sodium bicarbonate and a poured-bulk density of 1.0 to 1.2 grams per milliliter. Treatment rinses.(3) (i) An aqueous solution of acidulated phosphate fluoride derived from sodium fluoride acidulated with a mixture of sodium phosphate, monobasic, and phosphoric acid to a level of 0.1 molar phosphate ion and a pH of 3.0 to 4.5 and which yields an effective fluoride ion concentration of 0.02 percent. (ii) An aqueous solution of acidulated phosphate fluoride derived from sodium fluoride acidulated with a mixture of sodium phosphate, dibasic, and phosphoric acid to a pH of 3.5…
Package size limitation.(a) Due to the toxicity associated with fluoride active ingredients, the following package size limitations are required for anticaries drug products: Dentifrices.(1) Dentifrice (toothpastes and tooth powders) packages shall not contain more than 276 milligrams (mg) total fluorine per package. Preventive treatment gels and treatment rinses.(2) Preventive treatment gel and treatment rinse packages shall not contain more than 120 mg total fluorine per package. Exception.(3) Package size limitations do not apply to anticaries drug products marketed for professional office use only and labeled in accord with § 355.60. Tight container packaging.(b) To minimize moisture contamination, all fluoride powdered dentifrices shall be packaged in a tight container as defined as a container that protects the contents from contamination by extraneous liquids, solids, or vapors, from loss of the article, and from efflorescence, deliquescence, or evaporation under the ordinary or customary conditions of handling, shipment, storage, and distribution, and is capable of tight reclosure.
As used in this part: Abrasive.(a) Solid materials that are added to dentifrices to facilitate mechanical removal of dental plaque, debris, and stain from tooth surfaces. Anhydrous glycerin.(b) An ingredient that may be prepared by heating glycerin U.S.P. at 150 °C for 2 hours to drive off the moisture content. Anticaries drug.(c) A drug that aids in the prevention and prophylactic treatment of dental cavities (decay, caries). Dental caries.(d) A disease of calcified tissues of teeth characterized by demineralization of the inorganic portion and destruction of the organic matrix. Dentifrice.(e) An abrasive-containing dosage form (gel, paste, or powder) for delivering an anticaries drug to the teeth. Fluoride.(f) The inorganic form of the chemical element fluorine in combination with other elements. Fluoride ion.(g) The negatively charged atom of the chemical element fluorine. Fluoride supplement.(h) A special treatment rinse dosage form that is intended to be swallowed, and is promoted to health professionals for use in areas where the water supply contains 0 to 0.7 parts per million (ppm) fluoride ion. Preventive treatment gel.(i) A dosage form for delivering an…
Statement of identity.(a) The labeling of the product contains the established name of the drug, if any, and identifies the product as: (select one or both of the following: ‘anticavity’ or ‘fluoride’) (select one of the following as appropriate: “dentifrice,” “toothpaste,” “tooth polish,” “tooth powder;” (optional: “dental”) “preventive treatment gel;” or (optional: “treatment” or “dental”)) (select one of the following: “rinse,” “concentrated solution,” “rinse powder,” or “rinse effervescent tablets”). The word “mouthwash” may be substituted for the word “rinse” in this statement of identity if the product also has a cosmetic use, as defined in section 201(i) of the Federal Food, Drug, and Cosmetic Act (the act) (21 U.S.C. 321(i)). Indication.(b) The labeling of the product states, under the heading “Indication,” the following: “Aids in the prevention of dental (select one of the following: “cavities,” “decay,” “caries (decay),” or “caries (cavities)”). Other truthful and nonmisleading statements, describing only the indication for use that has been established and listed in this paragraph (b), may also be used, as provided in § 330.1(c)(2) of this chapter, subject to the…
In addition to the statement of identity required in § 355.50, the following statement shall be prominently placed on the principal display panel: “IMPORTANT: Read directions for proper use.”
(a) The labeling for anticaries fluoride treatment rinses identified in § 355.10(a)(3) and (c)(3) that are specially formulated so they may be swallowed (fluoride supplements) and are provided to health professionals (but not to the general public) may contain the following additional dosage information: Children 3 to under 14 years of age: As a supplement in areas where the water supply is nonfluoridated (less than 0.3 parts per million (ppm)), clean the teeth with a toothpaste and rinse with 5 milliliters (mL) of 0.02 percent or 10 mL of 0.01 percent fluoride ion rinse daily, then swallow. When the water supply contains 0.3 to 0.7 ppm fluoride ion, reduce the dose to 2.5 mL of 0.02 percent or 5 mL of 0.01 percent fluoride ion rinse daily. (b) The labeling for products marketed to health to health professionals in package sizes larger than those specified in § 355.20 shall include the statements: “For Professional Office Use Only” and “This product is not intended for home or unsupervised consumer use.”
Biological Testing Procedures for Fluoride Dentifrices(a) A fluoride dentifrice drug product shall meet the biological test requirements for animal caries reduction and one of the following tests: Enamel solubility reduction or fluoride enamel uptake. The testing procedures for these biological tests are labeled ; these testing procedures are on file under Docket No. 80N-0042 in the Division of Dockets Management (HFA-305), Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852, and are available on request to that office. (b) The United States Pharmacopeia fluoride dentifrice reference standards along with reference standard stability profiles (total fluoride, available fluoride ion, pH, and specific gravity) required to be used in the biological tests are available to any purchaser upon written request to the United States Pharmacopeial Convention, Inc., 1260 Twinbrook Parkway, Rockville, MD 20852. (c) Alternative testing procedures may be used. Any proposed modification or alternative testing procedures shall be submitted as a petition in accord with § 10.30 of this chapter. The petition should contain data to support the modification or data…
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